The Notch (N) signaling pathway plays a key role in mediating intercellular interactions underlying alternative cell fate decisions in groups of omnipotent cells in many tissues and species including Drosophila, Xenopus, humans, and mice. Inappropriate N activity has been associated with the formation of acute lymphoblastic leukemia in aberrations in chromosomal loci known to contain N homologs in humans have been correlated with certain cancers including ovarian carcinoma, acute myeloblastic leukemia and acute lymphoblastic leukemia. The primary transducer of the N signal is the transcription factor Suppressor of Hairless [Su(H)]. Recently, we have identified a novel, conserved Su(H) binding motif, the Su(H) "paired site" (SPS), in the promoters of a subset of Su(H)-dependent genes in both D. melanogaster and mice that play a positive role in the N pathway-responsive, Su(H)-mediated expression of these genes. Using both genetic and biochemical approaches, I propose to investigate the contribution of this SPS motif in N-pathway-mediated cell fate specification. using mechanosensory bristle formation in Drosophila melanogaster as a model system. Because of the conserved nature of this pathway, understanding the mechanism by which Su(H) regulates its target genes through the SPS in Drosophila should be applicable toward understanding the N-mediated cellular processes leading to tumorigenesis in humans.